EP0218970B1 - Chiral rhodium-diphosphine complexes for asymmetrical hydrogenation - Google Patents

Chiral rhodium-diphosphine complexes for asymmetrical hydrogenation Download PDF

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EP0218970B1
EP0218970B1 EP86113271A EP86113271A EP0218970B1 EP 0218970 B1 EP0218970 B1 EP 0218970B1 EP 86113271 A EP86113271 A EP 86113271A EP 86113271 A EP86113271 A EP 86113271A EP 0218970 B1 EP0218970 B1 EP 0218970B1
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aryl
lower alkyl
formula
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hydrogen
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EP0218970A2 (en
EP0218970A3 (en
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Emil Albin Dr. Broger
Yvo Dr. Crameri
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F Hoffmann La Roche AG
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    • B01J31/2404—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
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    • B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
    • B01J31/2495—Ligands comprising a phosphine-P atom and one or more further complexing phosphorus atoms covered by groups B01J31/1845 - B01J31/1885, e.g. phosphine/phosphinate or phospholyl/phosphonate ligands
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    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
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    • C07D307/30—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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    • C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
    • C07F15/0073—Rhodium compounds
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    • B01J2231/60—Reduction reactions, e.g. hydrogenation
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    • B01J2231/60—Reduction reactions, e.g. hydrogenation
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    • B01J2231/641—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes
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    • B01J2531/80—Complexes comprising metals of Group VIII as the central metal
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    • B01J31/1805—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms the ligands containing nitrogen
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    • B01J31/1875—Phosphinites (R2P(OR), their isomeric phosphine oxides (R3P=O) and RO-substitution derivatives thereof)

Definitions

  • the invention further relates to the production of the rhodium-diphosphine complexes of the formula I and their use for asymmetric hydrogenations.
  • Chiral rhodium-diphosphine complexes and their use in asymmetric hydrogenations are already known from the literature. These complexes are usually cationic or, if neutral, contain chlorine, bromine or iodine as ligand X.
  • the optical yields which are achieved when using such complexes in asymmetric hydrogenations are in the most favorable cases around 80-84%, in the case of the hydrogenation of ketopantolactone [J. Org. Chem., Vol. 43, No 18 (1978) 3444-3446].
  • Cationic rhodium complexes with a chiral PPM ligand are also known from J. Organometallic Chem., Vol. 218, No2, Sept. 1981, pages 249-260 and Vol. 288, No2, June 1985, pages C 37-C 39. or a ligand derived therefrom by substitution on the H atom of pyrrolidine, such as, for example, BPPM, optionally a further, neutral ligand and, in contrast to the present application, with BF4 ⁇ or ClO4 ⁇ as counterion.
  • EP-A-0158875 describes complexes which are very similar to the rhodium-diphosphine complexes claimed in the present application, but this reference is only a state of the art according to Art. 54 (3) EPUe, which has already been taken into account accordingly .
  • lower alkyl means straight-chain or branched alkyl groups having 1 to 9 carbon atoms, such as, for example, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, tert. Butyl, pentyl, hexyl, heptyl, octyl or nonyl and the like.
  • halogen means fluorine, chlorine, bromine and iodine, with fluorine being preferred.
  • perfluoro-C1 ⁇ 20-alkyl in the context of the present invention means both straight-chain and branched, optionally also optically active chains, it being not necessary for all hydrogen atoms to be replaced by fluorine atoms. If not all hydrogen atoms have been replaced by fluorine atoms, there is often in particular a terminal hydrogen atom available. If X is fixed on a carrier, this is done via a group -COA.
  • aryl used in connection with the compounds of the formula I means, in the context of the present invention, both aromatic hydrocarbons and aromatic heterocycles having 4 to 14 carbon atoms. Particularly suitable heteroatoms are oxygen and nitrogen. Furthermore, the rings can be both unsubstituted and substituted, preferred substituents being halogen, hydroxyl, lower alkyl, perfluoro-lower alkyl, lower alkoxy and formyl. An existing aryl group can also be complexed to a transition metal such as chromium, iron or even nickel.
  • aryl used below in connection with the compounds of the formula II means phenyl which, if appropriate in the para and / or meta position, has lower alkyl or lower alkoxy groups, preferably methyl or methoxy groups, or may also have di-lower alkylamino, preferably dimethylamino groups, and also a carboxy, carbamoyl, cyano or a lower alkoxycarbonyl group.
  • two aryl groups on the same phosphorus atom can be directly connected to one another via the o-position or else via a methylene, ethylene or propylene group.
  • aryloxy means groups in which the aryl radical has the previous meaning.
  • lower alkoxy means groups in which the alkyl radical has the previous meaning. Furthermore, the sign “ “that the corresponding residue is above the molecular level, while the symbol”"means that the corresponding residue is below the molecular level.
  • n means a number from 0 to 20, preferably from 1 to 12, in particular from 1 to 8.
  • neutral ligand in the context of the present invention means an easily replaceable ligand such as olefins, e.g. Ethylene, propylene, cyclooctene, 1,5-hexadiene, norbornadiene, 1,5-cyclooctadiene and the like, nitriles such as acetonitrile, benzonitrile, or also the solvent used, etc.
  • This ligand can be exchanged in the hydrogenation. If more than one such ligand is present, these can also be different from one another.
  • any diphosphine ligands known in connection with asymmetric hydrogenations which can optionally also be fixed on a support, can be used as chiral diphosphine ligands.
  • the ligands are known and easily accessible to those skilled in the art.
  • ligands in question within the scope of the present invention are known from: Marko, L. et al., Aspects of Homogenous Catalysis, 4 , 145-202 (1981); Japanese patent application No. 67411 of June 4, 1978 (Derwent 8180 C); German laid-open publication No. 2,161,200; European Patent Publication No. 104 375.
  • Particularly suitable and preferred ligands are, for example, the chiral phosphines of the general formula wherein R8 aryl and R9 represent the groups -CO-R10, -SO2-R10, -PO (R10) 2 or -PS (R10) 2, where R10 aryl, lower alkyl, di-arylamino, di-lower alkylamino, aryloxy or lower alkoxy mean, where the lower alkyl or alkoxy radicals have 1-9 carbon atoms and the term aryl stands for itself or in aryloxy for optionally substituted phenyl.
  • Preferred rhodium-diphosphine complexes of the formula I are those in which Z is the group represents and one of the substituents R1, R2 and R3 is the radical -OR7 and the other two fluorine, hydrogen, perfluoro-C1 ⁇ 20-alkyl or aryl, and those in which one of the substituents R1, R2 and R3 aryl and the two represent other fluorine, hydrogen or perfluoro-C1 ⁇ 20 alkyl, but at least one of them is fluorine.
  • the ligand X is chiral, it can be in racemic or preferably in optically active form.
  • Preferred diphosphine ligands of the formula II are those in which R8 is phenyl, p-tolyl, m-tolyl or 3,5-xylyl and R10 in the radicals R9 phenyl, p-tolyl, m-tolyl, p-lower. Alkoxycarbonylphenyl or tert. Butoxy means.
  • Particularly preferred phosphines are also those in which the radical R9 represents the group -PO (R10) 2.
  • diphosphine ligands (2S, 4S) -4- (di-m-tolylphosphino) -2 - [(di-m-tolylphosphino) methyl] -1- (diphenylphosphinoyl) pyrrolidine;
  • mCH3-POPPM (2S, 4S) -4- (Diphenylphosphino) -2 - [(diphenylphosphino) methyl] -1- (diphenylphosphinoyl) pyrrolidine:
  • POPPM (2S, 4S) -4- (di-p-tolylphosphino) -2 - [(di-p-tolylphosphino) methyl] -1- (diphenylphosphinoyl) pyrrolidine;
  • pCH3-POPPM (2S, 4S) -4- (Diphenylphosphino) -2 - [(di-m-toly
  • Particularly preferred rhodium-diphosphine complexes of the formula I are those in which one of the substituents R1, R2 and R3 is -OR7 and the other two are fluorine or one trifluoromethyl and the other is phenyl, and those in which one of the substituents R1, R2 and R3 Represent phenyl and the other two fluorine or one hydrogen and the other fluorine and the diphosphine ligand is mCH3-POPPM.
  • the complexes of the formulas are very particularly preferred: [Rh (C6F5-O-CF2-COO) (mcH3-POPPM) (L 0.1 or 2 )] 1 or 2 [Rh ((R) -C6H5-C (CF3) (OCH3) -COO) (mCH3-POPPM) (L 0,1 or 2 )] 1 or 2 [Rh (C6H5-CHF-COO) (mCH3-POPPM) (L 0.1 or 2 )] 1 or 2
  • the reactions of the rhodium complexes of the formulas III, IV, V and VI in accordance with reaction variants a) - d) can be carried out in a manner known per se. This is expediently carried out in an inert organic solvent. Examples include: aromatic hydrocarbons such as benzene, toluene, etc., esters such as ethyl acetate, etc., cyclic ethers such as tetrahydrofuran or dioxane, lower alcohols such as methanol, ethanol and the like, or mixtures thereof.
  • the reaction can take place at temperatures between about 0 ° C. to about 100 ° C., preferably at about 15 ° C. to about 60 ° C., but with the strict exclusion of oxygen.
  • salt containing anion X means in particular ammonium salts, alkali metal salts, alkaline earth metal salts and other suitable metal salts. Such salts are known substances. In order to increase the solubility of such salts in certain solvents, a suitable crown ether can optionally be added.
  • the rhodium-diphosphine complexes of the formula I are catalysts or precursors thereof. Since their exact chemical structure cannot be given with certainty, they are also characterized in that they are obtainable by reacting a rhodium complex of the formulas III-VI in accordance with the reactions a) to d) mentioned above.
  • the rhodium complexes of the formulas III, IV, V and VI used as starting materials are known substances or analogs of known substances which can easily be prepared analogously to the known ones.
  • the rhodium-diphosphine complexes of the formula I according to the invention serve as catalysts in asymmetric hydrogenations. They are particularly interesting in connection with the asymmetric hydrogenation of ⁇ , ⁇ -unsaturated acids and esters as well as of ⁇ -keto-carboxylic acids and esters and of ⁇ -keto-lactones. They are of particular interest for the asymmetric hydrogenation of dihydro-4,4-dimethyl-2,3-furandione (ketopantolactone) to the corresponding R- ( ⁇ -hydroxy- ⁇ , ⁇ -dimethyl- ⁇ -butyrolactone) [R - (-) -Pantolactone].
  • the complexes of the formula I can be added as such to a solution of an asymmetrically hydrogenated compound.
  • they can also be formed in situ in the presence of an asymmetrically hydrogenated compound will.
  • the asymmetric hydrogenations can be carried out in suitable organic solvents which are inert under the reaction conditions.
  • suitable organic solvents which are inert under the reaction conditions.
  • lower alkanols such as e.g. Methanol or ethanol
  • aromatic hydrocarbons such as benzene or toluene
  • cyclic ethers such as tetrahydrofuran or dioxane
  • esters such as e.g. Ethyl acetate or mixtures thereof and the like.
  • the ratio between rhodium and the ligands Y is advantageously between about 0.05 and about 5 moles, preferably between about 0.5 and about 2 moles of rhodium per mole of ligand.
  • the ratio between rhodium and the radical X is advantageously between about 0.01 and about 20, preferably between about 0.5 and about 10 moles of rhodium per mole of radical X.
  • the ratio between rhodium in the complexes of the formula I and to Hydrogenating compounds are expediently between about 0.00001 and about 5% by weight, preferably between about 0.0001 and about 0.01% by weight.
  • the asymmetric hydrogenations using the complexes of the formula I can expediently be carried out at temperatures from about 0 ° C. to about 100 ° C., preferably from about 20 ° C. to about 70 ° C. These hydrogenations are advantageously carried out under pressure, in particular under a pressure of about 1 to 100 bar, preferably 2 to 50 bar.
  • the enantiomeric composition (enantiomeric excess ee) was determined by gas chromatographic determination of (R) - and (S) -pantolactone on a 25m capillary column with a chiral phase (SP-300).
  • SP-300 gas chromatographic determination of (R) - and (S) -pantolactone on a 25m capillary column with a chiral phase (SP-300).
  • the optical rotations of (R) - (-) - pantolactone at 589 nm (D line) at 20 ° C and a concentration of 3% in ion-free water were also measured.
  • a 500 ml autoclave was charged with 40 g (0.31 mol) of ketopantolactone, 160 ml of toluene and 50 ml of the catalyst solution prepared according to Example 1.
  • the hydrogenation was carried out at 40 ° C, a constant pressure of 40 bar H2 and with intensive stirring. After 1 hour, the conversion was 99.8%.
  • the yellow hydrogenation solution was rinsed out of the autoclave and the autoclave was then rinsed three times with 50 ml of toluene.
  • the combined toluene solutions were evaporated on a rotary evaporator at 60 ° C./17 mbar.

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Abstract

Chiral diphosphinerhodium complexes of the formula <IMAGE> in which X, Y and L are as defined in Claim 1 and their preparation are described.

Description

Die vorliegende Erfindung betrifft neue chirale Rhodium-diphosphinkomplexe der allgemeinen Formel



        [Rh(X)(Y)(L0,1 oder 2)]1 oder 2   

I

worin X, welches gegebenenfalls auf einem Träger fixiert sein kann, einen Rest der Formel Z-COO⁻ darstellt, worin Z wiederum eine Gruppe

Figure imgb0001

oder Aryl bedeutet, worin

R¹, R², R³ =
Wasserstoff. Halogen, niederes Alkyl, Aryl-niederes Alkyl, Perfluor-C₁₋₂₀-Alkyl, Aryl oder die Gruppe -OR⁷, -(CH₂)n-COA oder AOC-(CF₂)n bedeuten, wobei wenigstens einer von R¹, R² und R³ -OR⁷ oder Aryl darstellt,
R⁴, R⁵, R⁶ =
Wasserstoff, Halogen, niederes Alkyl, Aryl-niederes Alkyl, Perfluor-C1-20-Alkyl, Aryl oder die Gruppe -(CH₂)n-COA oder AOC-(CF₂)n bedeuten
R⁷ =
Wasserstoff, niederes Alkyl, teilweise oder vollständig halogeniertes niederes Alkyl, Aryl oder Aryl-niederes Alkyl darstellt
A =
die Reste -OR oder -NR'₂ bedeutet
R =
Wasserstoff, niederes Alkyl, Aryl, Aryl-niederes Alkyl oder ein Kation bedeutet,
R' =
Wasserstoff, niederes Alkyl, Aryl oder Aryl-niederes Alkyl bedeutet,
n =
eine Zahl 0 bis 20 bedeutet, ferner Y einen chiralen Diphosphinliganden und L einen neutralen Liganden darstellen,
mit Ausnahme derjenigen Komplexe der Formel I, worin X, welches gegebenenfalls auf einem Träger fixiert sein kann, einen Rest der Formel Z-COO⁻ darstellt, worin Z wiederum die Gruppe
Figure imgb0002
Perfluorphenyl, Perfluorbiphenyl oder einen Rest der Formel
Figure imgb0003
bedeutet und R¹, R² und R³ Halogen, niederes Alkyl, Perfluorphenyl, Perfluor-C1-20-Alkyl, Wasserstoff oder die Gruppe -COA oder AOC-(CF₂)n- darstellen, worin A die Reste -OR oder -NR'₂ bedeutet, wobei jedoch wenigstens einer der Substituenten R¹, R² und R³ Fluor bedeutet, R Wasserstoff, niederes Alkyl oder ein Kation, R' Wasserstoff oder niederes Alkyl, und n eine Zahl 1 bis 20 bedeuten, wobei die niederen Alkylreste 1-9 Kohlenstoffatome aufweisen und der Ausdruck Aryl für gegebenenfalls substituierte aromatische Kohlenwasserstoffe oder aromatische Heterocyclen mit 4-14 Kohlenstoffatomen steht.The present invention relates to new chiral rhodium-diphosphine complexes of the general formula



[Rh (X) (Y) (L 0,1 or 2 )] 1 or 2

I.

wherein X, which may optionally be fixed on a support, represents a radical of the formula Z-COO⁻, wherein Z in turn is a group
Figure imgb0001
or aryl, wherein
R¹, R², R³ =
Hydrogen. Halogen, lower alkyl, aryl-lower alkyl, perfluoro-C₁₋₂₀-alkyl, aryl or the group -OR⁷, - (CH₂) n -COA or AOC- (CF₂) n mean, at least one of R¹, R² and R³ Represents -OR⁷ or aryl,
R⁴, R⁵, R⁶ =
Hydrogen, halogen, lower alkyl, aryl-lower alkyl, perfluoro-C 1-20 alkyl, aryl or the group - (CH₂) n -COA or AOC- (CF₂) n mean
R⁷ =
Represents hydrogen, lower alkyl, partially or fully halogenated lower alkyl, aryl or aryl lower alkyl
A =
the radicals -OR or -NR'₂ means
R =
Represents hydrogen, lower alkyl, aryl, aryl-lower alkyl or a cation,
R '=
Represents hydrogen, lower alkyl, aryl or aryl-lower alkyl,
n =
represents a number 0 to 20, furthermore Y represents a chiral diphosphine ligand and L represents a neutral ligand,
with the exception of those complexes of the formula I in which X, which may optionally be fixed on a support, represents a radical of the formula Z-COO⁻, in which Z in turn represents the group
Figure imgb0002
Perfluorophenyl, perfluorobiphenyl or a radical of the formula
Figure imgb0003
means and R¹, R² and R³ halogen, lower alkyl, perfluorophenyl, perfluoro-C 1-20 alkyl, hydrogen or the group -COA or AOC- (CF₂) n -, wherein A represents the radicals -OR or -NR'₂ means, however, at least one of the substituents R¹, R² and R³ is fluorine, R is hydrogen, lower Alkyl or a cation, R 'is hydrogen or lower alkyl, and n is a number from 1 to 20, where the lower alkyl radicals have 1-9 carbon atoms and the term aryl stands for optionally substituted aromatic hydrocarbons or aromatic heterocycles with 4-14 carbon atoms.

Die Erfindung betrifft ferner die Herstellung der Rhodium-diphosphinkomplexe der Formel I, sowie deren Verwendung für asymmetrische Hydrierungen.The invention further relates to the production of the rhodium-diphosphine complexes of the formula I and their use for asymmetric hydrogenations.

Aus der Literatur sind bereits chirale Rhodium-diphosphinkomplexe und deren Verwendung bei asymmetrischen Hydrierungen bekannt. Ueblicherweise sind diese Komplexe kationisch oder enthalten - falls neutral - als Ligand X Chlor, Brom oder Jod. Die optischen Ausbeuten welche bei der Verwendung derartiger Komplexe in asymmetrischen Hydrierungen erzielt werden, liegen in den günstigsten Fällen bei etwa 80-84%, im Falle der Hydrierung von Ketopantolacton [J. Org. Chem., Vol.43, No 18 (1978) 3444-3446].Chiral rhodium-diphosphine complexes and their use in asymmetric hydrogenations are already known from the literature. These complexes are usually cationic or, if neutral, contain chlorine, bromine or iodine as ligand X. The optical yields which are achieved when using such complexes in asymmetric hydrogenations are in the most favorable cases around 80-84%, in the case of the hydrogenation of ketopantolactone [J. Org. Chem., Vol. 43, No 18 (1978) 3444-3446].

Aus J. Organometallic Chem., Bd. 218, No2, Sept. 1981, Seiten 249-260 und Bd. 288, No2, Juni 1985, Seiten C 37-C 39 sind weiterhin kationische Rhodiumkomplexe bekannt, mit einem chiralen PPM-Liganden, bzw. einem davon durch Substitution am H-Atom des Pyrrolidins abgeleiteten Liganden, wie beispielsweise BPPM, gegebenenfalls einem weiteren, neutralen Liganden und, im Unterschied zur vorliegenden Anmeldung, mit BF₄⊖ beziehungsweise ClO₄⊖ als Gegenion.Cationic rhodium complexes with a chiral PPM ligand are also known from J. Organometallic Chem., Vol. 218, No2, Sept. 1981, pages 249-260 and Vol. 288, No2, June 1985, pages C 37-C 39. or a ligand derived therefrom by substitution on the H atom of pyrrolidine, such as, for example, BPPM, optionally a further, neutral ligand and, in contrast to the present application, with BF₄ ⊖ or ClO₄ ⊖ as counterion.

Ausserdem sind in EP-A-0158875 den in vorliegender Anmeldung beanspruchten Rhodium-diphosphinkomplexen sehr ähnliche Komplexe beschrieben, wobei es sich bei dieser Literaturstelle jedoch lediglich um einen Stand der Technik nach Art. 54(3) EPUe handelt, welchem bereits entsprechend Rechnung getragen wurde.In addition, EP-A-0158875 describes complexes which are very similar to the rhodium-diphosphine complexes claimed in the present application, but this reference is only a state of the art according to Art. 54 (3) EPUe, which has already been taken into account accordingly .

Ueberraschenderweise wurde nun gefunden, dass die erfindungsgemässen Rhodium-diphosphinkomplexe der Formel I im Vergleich zu den vorbekannten erheblich aktiver und enantioselektiver sind, was insbesondere dazu führt, dass durch ihre Verwendung erheblich geringere Katalysatormengen verwendet werden können, kürzere Reaktionszeiten möglich sind und optische Ausbeuten von über 95% erzielt werden können.Surprisingly, it has now been found that the rhodium-diphosphine complexes of the formula I according to the invention are considerably more active and enantioselective in comparison with the previously known ones, which leads in particular to the fact that by their use considerably smaller amounts of catalyst can be used, shorter reaction times are possible and optical yields of over 95% can be achieved.

Der Ausdruck "niederes Alkyl" bedeutet im Rahmen der vorliegenden Erfindung geradkettige oder verzweigte Alkylgruppen mit 1 bis 9 Kohlenstoffatomen wie z.B. Methyl, Aethyl, Propyl, Isopropyl, n-Butyl, Isobutyl, tert. Butyl, Pentyl, Hexyl, Heptyl, Octyl oder Nonyl und dergleichen. Der Ausdruck "Halogen" bedeutet Fluor, Chlor, Brom und Jod, wobei Fluor bevorzugt ist. Der Ausdruck "Perfluor-C₁₋₂₀-Alkyl" bedeutet im Rahmen der vorliegenden Erfindung sowohl geradkettige, als auch verzweigte, gegebenenfalls auch optisch aktive Ketten, wobei nicht unbedingt sämtliche Wasserstoffatome durch Fluoratome ersetzt sein müssen. Falls nicht alle Wasserstoffatome durch Fluoratome ersetzt sind, so ist häufig insbesondere noch ein endständiges Wasserstoffatom vorhanden. Sofern X auf einem Träger fixiert ist, erfolgt dies über eine Gruppe -COA.In the context of the present invention, the term “lower alkyl” means straight-chain or branched alkyl groups having 1 to 9 carbon atoms, such as, for example, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, tert. Butyl, pentyl, hexyl, heptyl, octyl or nonyl and the like. The term "halogen" means fluorine, chlorine, bromine and iodine, with fluorine being preferred. The term "perfluoro-C₁₋₂₀-alkyl" in the context of the present invention means both straight-chain and branched, optionally also optically active chains, it being not necessary for all hydrogen atoms to be replaced by fluorine atoms. If not all hydrogen atoms have been replaced by fluorine atoms, there is often in particular a terminal hydrogen atom available. If X is fixed on a carrier, this is done via a group -COA.

Der im Zusammenhang mit den Verbindungen der Formel I verwendete Ausdruck "Aryl" bedeutet, im Rahmen der vorliegenden Erfindung, sowohl aromatische Kohlenwasserstoffe als auch aromatische Heterocyclen mit 4 bis 14 Kohlenstoffatomen. Als Heteroatome kommen insbesondere in Betracht Sauerstoff und Stickstoff. Weiterhin können die Ringe sowohl unsubstituiert als auch substituiert sein, wobei als Substituenten bevorzugt in Betracht kommen, Halogen, Hydroxy, niederes Alkyl, Perfluor-niederes Alkyl, niederes Alkoxy und Formyl. Eine vorhandene Arylgruppe kann zudem an ein Uebergangsmetall wie Chrom, Eisen oder auch Nickel komplexiert sein.The term "aryl" used in connection with the compounds of the formula I means, in the context of the present invention, both aromatic hydrocarbons and aromatic heterocycles having 4 to 14 carbon atoms. Particularly suitable heteroatoms are oxygen and nitrogen. Furthermore, the rings can be both unsubstituted and substituted, preferred substituents being halogen, hydroxyl, lower alkyl, perfluoro-lower alkyl, lower alkoxy and formyl. An existing aryl group can also be complexed to a transition metal such as chromium, iron or even nickel.

Der im nachfolgenden, im Zusammenhang mit den Verbindungen der Formel II verwendete Ausdruck "Aryl" bedeutet im Rahmen der vorliegenden Erfindung Phenyl, welches gegebenenfalls in para- und/oder meta-Stellung niedere Alkyl- oder niedere Alkoxygruppen, vorzugsweise Methyl- oder Methoxygruppen, oder auch di-niederes Alkylamino, vorzugsweise Dimethylaminogruppen, sowie eine Carboxy-, Carbamoyl-, Cyano- oder eine niedere Alkoxycarbonylgruppe aufweisen kann. Zudem können zwei Arylgruppen am gleichen Phosphoratom über die o-Stellung direkt miteinander verbunden sein oder auch über eine Methylen-, Aethylen- oder Propylengruppe. Der Ausdruck "Aryloxy" bedeutet Gruppen, in denen der Arylrest die vorhergehende Bedeutung hat.In the context of the present invention, the term “aryl” used below in connection with the compounds of the formula II means phenyl which, if appropriate in the para and / or meta position, has lower alkyl or lower alkoxy groups, preferably methyl or methoxy groups, or may also have di-lower alkylamino, preferably dimethylamino groups, and also a carboxy, carbamoyl, cyano or a lower alkoxycarbonyl group. In addition, two aryl groups on the same phosphorus atom can be directly connected to one another via the o-position or else via a methylene, ethylene or propylene group. The term "aryloxy" means groups in which the aryl radical has the previous meaning.

Der Ausdruck "niederes Alkoxy" bedeutet Gruppen, in denen der Alkylrest die vorhergehende Bedeutung hat. Weiterhin bedeutet das Zeichen "

Figure imgb0004
", dass sich der entsprechende Rest oberhalb der Molekülebene befindet, während das Zeichen " " bedeutet, dass sich der entsprechende Rest unterhalb der Molekülebene befindet. Der Buchstabe n bedeutet eine Zahl von 0 bis 20, vorzugsweise von 1 bis 12, insbesondere von 1 bis 8.The term "lower alkoxy" means groups in which the alkyl radical has the previous meaning. Furthermore, the sign "
Figure imgb0004
"that the corresponding residue is above the molecular level, while the symbol""means that the corresponding residue is below the molecular level. The letter n means a number from 0 to 20, preferably from 1 to 12, in particular from 1 to 8.

Der Ausdruck "neutraler Ligand" bedeutet im Rahmen der vorliegenden Erfindung einen leicht austauschbaren Liganden wie Olefine, z.B. Aethylen, Propylen, Cycloocten, 1,5-Hexadien, Norbornadien, 1,5-Cyclooctadien und dergleichen, Nitrile wie Acetonitril, Benzonitril, oder auch das verwendete Lösungsmittel usw. Dieser Ligand kann bei der Hydrierung ausgetauscht werden. Falls mehr als ein solcher Ligand vorhanden ist, können diese auch voneinander verschieden sein.The term "neutral ligand" in the context of the present invention means an easily replaceable ligand such as olefins, e.g. Ethylene, propylene, cyclooctene, 1,5-hexadiene, norbornadiene, 1,5-cyclooctadiene and the like, nitriles such as acetonitrile, benzonitrile, or also the solvent used, etc. This ligand can be exchanged in the hydrogenation. If more than one such ligand is present, these can also be different from one another.

Als chirale Diphosphinliganden können im Prinzip beliebige, im Zusammenhang mit asymmetrischen Hydrierungen bekannte Diphosphinliganden, welche gegebenenfalls auch auf einem Träger fixiert sein können, verwendet werden. Der artige Liganden sind bekannt und dem Fachmann leicht zugänglich. Beispielsweise sind im Rahmen der vorliegenden Erfindung in Frage kommende Liganden bekannt aus: Marko, L. et al., Aspects of Homogenous Catalysis, 4, 145-202 (1981); Japanische Patentanmeldung No. 67411 vom 4.6.1978 (Derwent 8180 C); deutsche Offenlegungsschrift No. 2 161 200; Europäische Patentpublikation No. 104 375. Besonders geeignete und bevorzugte Liganden sind z.B. die chiralen Phosphine der allgemeinen Formel

Figure imgb0005

worin R⁸ Aryl und R⁹ die Gruppen -CO-R¹⁰, -SO₂-R¹⁰, -PO(R¹⁰)₂ oder -PS(R¹⁰)₂ darstellen, wobei R¹⁰ Aryl, niederes Alkyl, di-Arylamino, di-niederes Alkylamino, Aryloxy oder niederes Alkoxy bedeuten, wobei die niederen Alkyl- bzw. Alkoxyreste 1-9 Kohlenstoffatome aufweisen und der Ausdruck Aryl für sich oder in Aryloxy für gegebenenfalls substituiertes Phenyl steht.In principle, any diphosphine ligands known in connection with asymmetric hydrogenations, which can optionally also be fixed on a support, can be used as chiral diphosphine ligands. The ligands are known and easily accessible to those skilled in the art. For example, ligands in question within the scope of the present invention are known from: Marko, L. et al., Aspects of Homogenous Catalysis, 4 , 145-202 (1981); Japanese patent application No. 67411 of June 4, 1978 (Derwent 8180 C); German laid-open publication No. 2,161,200; European Patent Publication No. 104 375. Particularly suitable and preferred ligands are, for example, the chiral phosphines of the general formula
Figure imgb0005
wherein R⁸ aryl and R⁹ represent the groups -CO-R¹⁰, -SO₂-R¹⁰, -PO (R¹⁰) ₂ or -PS (R¹⁰) ₂, where R¹⁰ aryl, lower alkyl, di-arylamino, di-lower alkylamino, aryloxy or lower alkoxy mean, where the lower alkyl or alkoxy radicals have 1-9 carbon atoms and the term aryl stands for itself or in aryloxy for optionally substituted phenyl.

Bevorzugte Rhodium-diphosphinkomplexe der Formel I sind solche, worin Z die Gruppe

Figure imgb0006

darstellt und einer der Substituenten R¹, R² und R³ den Rest -OR⁷ und die beiden anderen Fluor, Wasserstoff, Perfluor-C₁₋₂₀-Alkyl oder Aryl bedeuten, sowie die jenigen, worin einer der Substituenten R¹, R² und R³ Aryl und die beiden anderen Fluor, Wasserstoff oder Perfluor-C₁₋₂₀-Alkyl darstellen, wobei jedoch wenigstens einer davon Fluor bedeutet. Falls der Ligand X chiral ist, kann dieser in racemischer oder bevorzugt in optisch aktiver Form vorliegen.Preferred rhodium-diphosphine complexes of the formula I are those in which Z is the group
Figure imgb0006
represents and one of the substituents R¹, R² and R³ is the radical -OR⁷ and the other two fluorine, hydrogen, perfluoro-C₁₋₂₀-alkyl or aryl, and those in which one of the substituents R¹, R² and R³ aryl and the two represent other fluorine, hydrogen or perfluoro-C₁₋₂₀ alkyl, but at least one of them is fluorine. If the ligand X is chiral, it can be in racemic or preferably in optically active form.

Bevorzugte Diphosphinliganden der Formel II sind solche, worin R⁸ Phenyl, p-Tolyl, m-Tolyl oder 3,5-Xylyl darstellt und R¹⁰ in den Resten R⁹ Phenyl, p-Tolyl, m-Tolyl, p-nied. Alkoxycarbonylphenyl oder tert. Butoxy bedeutet. Besonders bevorzugte Phosphine sind zudem die jenigen, worin der Rest R⁹ die Gruppe -PO(R¹⁰)₂ darstellt. Als Beispiele von bevorzugten Diphosphinliganden können folgende genannt werden:
   (2S,4S)-4-(Di-m-Tolylphosphino)-2-[(di-m-tolylphosphino) methyl]-1-(diphenylphosphinoyl)-pyrrolidin; (mCH₃-POPPM)
   (2S,4S)-4-(Diphenylphosphino)-2-[(diphenylphosphino) methyl]-1-(diphenylphosphinoyl)-pyrrolidin: (POPPM)
   (2S,4S)-4-(Di-p-Tolylphosphino)-2-[(di-p-tolylphosphino) methyl]-1-(diphenylphosphinoyl)-pyrrolidin; (pCH₃-POPPM)
   (2S,4S)-4-(Diphenylphosphino)-2-[(diphenylphosphino) methyl]-1-(di-p-carbomethoxyphenylphosphinoyl)-pyrrolidin;
   (2S,4S)-4-(Diphenylphosphino)-2-[(diphenylphosphino) methyl]-1-(tert. butoxycarbonyl)-pyrrolidin; (BPPM)
   (2S,4S)-4-(Di-m-Tolylphosphino)-2-[(di-m-tolylphosphino) methyl]-1-(tert. butoxycarbonyl)-pyrrolidin: (mCH₃-BPPM)Preferred diphosphine ligands of the formula II are those in which R⁸ is phenyl, p-tolyl, m-tolyl or 3,5-xylyl and R¹⁰ in the radicals R⁹ phenyl, p-tolyl, m-tolyl, p-lower. Alkoxycarbonylphenyl or tert. Butoxy means. Particularly preferred phosphines are also those in which the radical R⁹ represents the group -PO (R¹⁰) ₂. The following may be mentioned as examples of preferred diphosphine ligands:
(2S, 4S) -4- (di-m-tolylphosphino) -2 - [(di-m-tolylphosphino) methyl] -1- (diphenylphosphinoyl) pyrrolidine; (mCH₃-POPPM)
(2S, 4S) -4- (Diphenylphosphino) -2 - [(diphenylphosphino) methyl] -1- (diphenylphosphinoyl) pyrrolidine: (POPPM)
(2S, 4S) -4- (di-p-tolylphosphino) -2 - [(di-p-tolylphosphino) methyl] -1- (diphenylphosphinoyl) pyrrolidine; (pCH₃-POPPM)
(2S, 4S) -4- (Diphenylphosphino) -2 - [(diphenylphosphino) methyl] -1- (di-p-carbomethoxyphenylphosphinoyl) pyrrolidine;
(2S, 4S) -4- (diphenylphosphino) -2 - [(diphenylphosphino) methyl] -1- (tert-butoxycarbonyl) pyrrolidine; (BPPM)
(2S, 4S) -4- (Di-m-tolylphosphino) -2 - [(di-m-tolylphosphino) methyl] -1- (tert. butoxycarbonyl) pyrrolidine: (mCH₃-BPPM)

Besonders bevorzugte Rhodium-diphosphinkomplexe der Formel I sind diejenigen, worin einer der Substituenten R¹, R² und R³ den Rest -OR⁷ und die beiden anderen Fluor oder einer Trifluormethyl und der andere Phenyl bedeuten, sowie diejenigen, worin einer der Substituenten R¹, R² und R³ Phenyl und die beiden anderen Fluor oder einer Wasserstoff und der andere Fluor darstellen und der Diphosphinligand mCH₃-POPPM ist. Ganz besonders bevorzugt sind die Komplexe der Formeln:



        [Rh(C₆F₅-O-CF₂-COO)(mcH₃-POPPM)(L0,1 oder 2)]1 oder 2




        [Rh((R)-C₆H₅-C(CF₃)(OCH₃)-COO)(mCH₃-POPPM)(L0,1 oder 2)]1 oder 2




        [Rh(C₆H₅-CHF-COO)(mCH₃-POPPM)(L0,1 oder 2)]1 oder 2


Particularly preferred rhodium-diphosphine complexes of the formula I are those in which one of the substituents R¹, R² and R³ is -OR⁷ and the other two are fluorine or one trifluoromethyl and the other is phenyl, and those in which one of the substituents R¹, R² and R³ Represent phenyl and the other two fluorine or one hydrogen and the other fluorine and the diphosphine ligand is mCH₃-POPPM. The complexes of the formulas are very particularly preferred:



[Rh (C₆F₅-O-CF₂-COO) (mcH₃-POPPM) (L 0.1 or 2 )] 1 or 2




[Rh ((R) -C₆H₅-C (CF₃) (OCH₃) -COO) (mCH₃-POPPM) (L 0,1 or 2 )] 1 or 2




[Rh (C₆H₅-CHF-COO) (mCH₃-POPPM) (L 0.1 or 2 )] 1 or 2


Die erfindungsgmässen Rhodium-diphosphinkomplexe der Formel I können in an sich bekannter Weise hergestellt werden. Sie können beispielsweise dadurch hergestellt werden. dass man

  • a) einen Rhodiumkomplex der Formel



            [Rh (X) (Lm)]1 oder 2   III



    worin X und L obige Bedeutung haben, und m eine Zahl von 1 bis 4 bedeutet,
    mit einem chiralen Diphosphinliganden umsetzt, oder
  • b) einen Rhodiumkomplex der Formel



            [Rh (Lm+1)] ⁺ A ⁻   IV



    worin L und m obige Bedeutung haben und A⁻ ein Anion, insbesondere BF₄ ⁻, ClO₄ ⁻, PF₆ ⁻ oder B(C₆H₅)₄ ⁻ darstellt,
    mit einem chiralen Diphosphinliganden und einem das Anion X enthaltenden Salz umsetzt, oder
  • c) einen Rhodium-diphosphinkomplex der Formel



            [Rh (Lp) (Y)] ⁺ A⁻   V



    worin L, Y und A⁻ obige Bedeutung haben und p eine Zahl von 1 bis 3 darstellt,
    mit einem das Anion X enthaltenden Salz umsetzt, oder
  • d) einen chiralen Rhodium-diphosphinkomplex der Formel



            [Rh (X¹) (L1 oder 2) (Y)]   VI



    worin X¹ Halogen bedeutet und L und Y obige Bedeutung haben,
    mit einem Silbersalz oder Thalliumsalz der Formel



            Ag - X oder Tl - X   VII



    worin X obige Bedeutung hat,
umsetzt.The rhodium-diphosphine complexes of the formula I according to the invention can be prepared in a manner known per se. For example, they can be produced by this. that he
  • a) a rhodium complex of the formula



    [Rh (X) (L m )] 1 or 2 III



    where X and L have the above meaning, and m is a number from 1 to 4,
    reacted with a chiral diphosphine ligand, or
  • b) a rhodium complex of the formula



    [Rh (L m + 1 )] ⁺ A ⁻ IV



    in which L and m have the above meaning and A⁻ is an anion, in particular BF₄ ⁻, ClO₄ ⁻, PF₆ ⁻ or B (C₆H₅) ₄ ⁻,
    with a chiral diphosphine ligand and an anion X containing salt, or
  • c) a rhodium-diphosphine complex of the formula



    [Rh (L p ) (Y)] ⁺ A⁻ V



    where L, Y and A⁻ have the above meaning and p represents a number from 1 to 3,
    with a salt containing the anion X, or
  • d) a chiral rhodium-diphosphine complex of the formula



    [Rh (X¹) (L 1 or 2 ) (Y)] VI



    where X¹ is halogen and L and Y are as defined above,
    with a silver salt or thallium salt of the formula



    Ag - X or Tl - X VII



    where X has the above meaning,
implements.

Die Umsetzungen der Rhodiumkomplexe der Formeln III, IV, V und VI gemäss den Reaktionsvarianten a) - d) können in an sich bekannter Weise durchgeführt werden. Zweckmässig erfolgt dies in einem inerten organischen Lösungsmittel. Als Beispiele hierfür können genannt werden: aromatische Kohlenwasserstoffe wie Benzol, Toluol usw., Ester wie Essigester, usw., cyclische Aether wie Tetrahydrofuran oder Dioxan, niedere Alkohole wie Methanol, Aethanol und dergleichen oder auch Gemische hiervon. Die Umsetzung kann bei Temperaturen zwischen etwa 0°C bis etwa 100°C, vorzugsweise bei etwa 15°C bis etwa 60°C erfolgen, jedoch unter striktem Ausschluss von Sauerstoff.The reactions of the rhodium complexes of the formulas III, IV, V and VI in accordance with reaction variants a) - d) can be carried out in a manner known per se. This is expediently carried out in an inert organic solvent. Examples include: aromatic hydrocarbons such as benzene, toluene, etc., esters such as ethyl acetate, etc., cyclic ethers such as tetrahydrofuran or dioxane, lower alcohols such as methanol, ethanol and the like, or mixtures thereof. The reaction can take place at temperatures between about 0 ° C. to about 100 ° C., preferably at about 15 ° C. to about 60 ° C., but with the strict exclusion of oxygen.

Der Ausdruck "das Anion X enthaltende Salz" bedeutet im Rahmen der vorliegenden Erfindung insbesondere Ammoniumsalze, Alkalimetallsalze, Erdalkalimetallsalze sowie andere geeignete Metallsalze. Derartige Salze sind bekannte Substanzen. Um die Löslichkeit derartiger Salze in gewissen Lösungsmitteln zu erhöhen kann gegebenenfalls ein geeigneter Kronenäther zugesetzt werden.In the context of the present invention, the term “salt containing anion X” means in particular ammonium salts, alkali metal salts, alkaline earth metal salts and other suitable metal salts. Such salts are known substances. In order to increase the solubility of such salts in certain solvents, a suitable crown ether can optionally be added.

Bei den Rhodium-diphosphinkomplexen der Formel I handelt es sich um Katalysatoren bzw. um Vorstufen hiervon. Da deren genaue chemische Struktur nicht mit Sicherheit angegeben werden kann, sind sie auch dadurch gekennzeichnet, dass sie erhältlich sind, durch Umsetzung eines Rhodiumkomplexes der Formeln III-VI gemäss den vorhergehend erwähnten Reaktionen a) bis d).The rhodium-diphosphine complexes of the formula I are catalysts or precursors thereof. Since their exact chemical structure cannot be given with certainty, they are also characterized in that they are obtainable by reacting a rhodium complex of the formulas III-VI in accordance with the reactions a) to d) mentioned above.

Die als Ausgangsmaterialien verwendeten Rhodiumkomplexe der Formeln III, IV, V und VI sind bekannte Substanzen oder Analoge bekannter Substanzen, welche leicht in Analogie zu den bekannten hergestellt werden können.The rhodium complexes of the formulas III, IV, V and VI used as starting materials are known substances or analogs of known substances which can easily be prepared analogously to the known ones.

Wie bereits erwähnt dienen die erfindungsgemässen Rhodium-diphosphinkomplexe der Formel I als Katalysatoren bei asymmetrischen Hydrierungen. Besonders interessant sind sie im Zusammenhang mit der asymmetrischen Hydrierung von α,β-ungesättigten Säuren und Estern sowie von α-Keto-carbonsäuren und Estern und von α-Keto-Lactonen. Insbesondere sind sie von Interesse zur asymmetrischen Hydrierung von Dihydro-4,4-dimethyl-2,3-furandion (Ketopantolacton) zum entsprechenden R-(α-Hydroxy-β,β-dimethyl-γ-butyrolacton)[R-(-)-Pantolacton].As already mentioned, the rhodium-diphosphine complexes of the formula I according to the invention serve as catalysts in asymmetric hydrogenations. They are particularly interesting in connection with the asymmetric hydrogenation of α, β-unsaturated acids and esters as well as of α-keto-carboxylic acids and esters and of α-keto-lactones. They are of particular interest for the asymmetric hydrogenation of dihydro-4,4-dimethyl-2,3-furandione (ketopantolactone) to the corresponding R- (α-hydroxy-β, β-dimethyl-γ-butyrolactone) [R - (-) -Pantolactone].

Zur Durchführung der erwähnten asymmetrischen Hydrierungen können die Komplexe der Formel I als solche zu einer Lösung einer asymmetrisch zu hydrierenden Verbindung gegeben werden. Andererseits können sie auch in situ in Gegenwart einer asymmetrisch zu hydrierenden Verbindung gebildet werden.To carry out the asymmetric hydrogenations mentioned, the complexes of the formula I can be added as such to a solution of an asymmetrically hydrogenated compound. On the other hand, they can also be formed in situ in the presence of an asymmetrically hydrogenated compound will.

Die asymmetrischen Hydrierungen können in geeigneten, unter den Reaktionsbedingungen inerten organischen Lösungsmitteln durchgeführt werden. Als solche können insbesondere genannt werden niedere Alkanole wie z.B. Methanol oder Aethanol, aromatische Kohlenwasserstoffe wie Benzol oder Toluol, cyclische Aether wie Tetrahydrofuran oder Dioxan, Ester wie z.B. Essigester oder auch Gemische hiervon und dergleichen. Das Verhältnis zwischen Rhodium und den Liganden Y liegt zweckmässig zwischen etwa 0,05 und etwa 5 Mol, vorzugsweise zwischen etwa 0,5 und etwa 2 Mol Rhodium pro Mol Ligand. Das Verhälnis zwischen Rhodium und dem Rest X liegt zweckmässig zwischen etwa 0,01 und etwa 20, vorzugsweise zwischen etwa 0,5 und etwa 10 Mol Rhodium pro Mol Rest X. Das Verhältnis zwischen Rhodium, in den Komplexen der Formel I, und den zu hydrierenden Verbindungen liegt zweckmässig zwischen etwa 0,00001 und etwa 5 Gew.%, vorzugsweise zwischen etwa 0,0001 und etwa 0,01 Gew.%.The asymmetric hydrogenations can be carried out in suitable organic solvents which are inert under the reaction conditions. As such, lower alkanols such as e.g. Methanol or ethanol, aromatic hydrocarbons such as benzene or toluene, cyclic ethers such as tetrahydrofuran or dioxane, esters such as e.g. Ethyl acetate or mixtures thereof and the like. The ratio between rhodium and the ligands Y is advantageously between about 0.05 and about 5 moles, preferably between about 0.5 and about 2 moles of rhodium per mole of ligand. The ratio between rhodium and the radical X is advantageously between about 0.01 and about 20, preferably between about 0.5 and about 10 moles of rhodium per mole of radical X. The ratio between rhodium in the complexes of the formula I and to Hydrogenating compounds are expediently between about 0.00001 and about 5% by weight, preferably between about 0.0001 and about 0.01% by weight.

Die asymmetrischen Hydrierungen unter Verwendung der Komplexe der Formel I können zweckmässig bei Temperaturen von etwa 0°C bis etwa 100°C, vorzugsweise von etwa 20°C bis etwa 70°C, durchgeführt werden. Diese Hydrierungen erfolgen zweckmässig unter Druck, insbesondere unter einem Druck von etwa 1 bis 100 bar, vorzugsweise 2 bis 50 bar.The asymmetric hydrogenations using the complexes of the formula I can expediently be carried out at temperatures from about 0 ° C. to about 100 ° C., preferably from about 20 ° C. to about 70 ° C. These hydrogenations are advantageously carried out under pressure, in particular under a pressure of about 1 to 100 bar, preferably 2 to 50 bar.

Die folgenden Beispiele dienen zur Erläuterung der Erfindung und stellen keinerlei Einschränkung hiervon dar.The following examples serve to illustrate the invention and do not constitute any restriction thereof.

In diesen Beispielen haben die verwendeten Abkürzungen folgende Bedeutung:
   COD = 1,5-Cyclooctadien
   BPPM; mCH₃-POPPM: auf Seite 6 erwähnte Diphosphine.In these examples, the abbreviations used have the following meanings:
COD = 1,5-cyclooctadiene
BPPM; mCH₃-POPPM: diphosphines mentioned on page 6.

Die enantiomere Zusammensetzung (Enantiomerenüberschuss e.e.) wurde durch gaschromatographische Bestimmung von (R)- und (S)-Pantolacton auf einer 25m Kapillarsäule mit chiraler Phase (SP-300) bestimmt. In mehreren Fällen wurden zusätzlich die optischen Drehungen von (R)-(-)-Pantolacton bei 589 nm (D-Linie) bei 20°C und einer Konzentration von 3% in ionenfreiem Wasser gemessen. Die Werte für die optischen Reinheiten basieren auf [α] 20 D

Figure imgb0007
= -51,6° (c=3, H₂O)
für reinstes (R)-(-)-Pantolacton.The enantiomeric composition (enantiomeric excess ee) was determined by gas chromatographic determination of (R) - and (S) -pantolactone on a 25m capillary column with a chiral phase (SP-300). In several cases, the optical rotations of (R) - (-) - pantolactone at 589 nm (D line) at 20 ° C and a concentration of 3% in ion-free water were also measured. The optical purity values are based on [α] 20th D
Figure imgb0007
 = -51.6 ° (c = 3, H₂O)
for the purest (R) - (-) - pantolactone.

Beispiel 1example 1

In einer Glove-Box (O₂-Gehalt <1 ppm) wurden in einem 100 ml Glaskolben 254,2 mg (0,389 mMol) einer 40%igen wässerigen Tetrabutylammoniumhydroxid-Lösung, 108,2 mg (0,389 mMol) Perfluorphenoxyessigsäure, 157,8 mg (0,389 mMol) Bis-(1,5-Cyclooctadien)-rhodium(I)tetrafluoroborat und 281,7 mg (0,389 mMol) (2S,4S)-4-(Di-m-Tolylphosphino)-2-[(di-m -tolylphosphino)methyl]-1-(diphenylphosphinoyl)-pyrrolidin (mCH₃-POPPM) in 50 ml Toluol suspendiert. Die Suspension wurde anschliessend während 16 Stunden bei 22-25°C gerührt, wobei sich eine orange-rote, nahezu klare Katalysatorlösung bildete.In a glove box (O₂ content <1 ppm) were in a 100 ml glass flask 254.2 mg (0.389 mmol) of a 40% aqueous tetrabutylammonium hydroxide solution, 108.2 mg (0.389 mmol) perfluorophenoxyacetic acid, 157.8 mg (0.389 mmol) bis- (1,5-cyclooctadiene) rhodium (I) tetrafluoroborate and 281.7 mg (0.389 mmol) (2S, 4S) -4- (Di-m-tolylphosphino) -2 - [(di- m -tolylphosphino) methyl] -1- (diphenylphosphinoyl) pyrrolidine (mCH₃-POPPM) suspended in 50 ml of toluene. The suspension was then stirred at 22-25 ° C. for 16 hours, an orange-red, almost clear catalyst solution being formed.

Beispiel 2Example 2

In einer Glove-Box (O₂-Gehalt <1 ppm) wurde ein 500 ml-Autoklav mit 40 g (0,31 Mol) Ketopantolacton, 160 ml Toluol und 50 ml nach Beispiel 1 hergestellter Katalysatorlösung beladen. Die Hydrierung wurde bei 40°C, einem konstanten Druck von 40 bar H₂ und unter intensivem Rühren durchgeführt. Nach 1 Stunde betrug der Umsatz 99.8%. Nach total 4 Stunden Hydrierzeit wurde die gelbe Hydrierlösung aus dem Autoklaven gespült und der Autoklav anschliessend dreimal mit je 50 ml Toluol nachgespült. Die vereinigten Toluollösungen wurden am Rotationsverdampfer bei 60°C/17 mbar eingedampft. Der Rückstand (42 g) wurde bei 130-150°C Badtemperatur und 12 mbar destilliert. Man erhielt 40,3 g (99,3%) (R)-α-Hydroxy-β,β-dimethyl-γ-butyrolacton (= (R)-(-)-Pantolacton), mit einer optischen Reinheit von 92,8% e.e.In a glove box (O₂ content <1 ppm), a 500 ml autoclave was charged with 40 g (0.31 mol) of ketopantolactone, 160 ml of toluene and 50 ml of the catalyst solution prepared according to Example 1. The hydrogenation was carried out at 40 ° C, a constant pressure of 40 bar H₂ and with intensive stirring. After 1 hour, the conversion was 99.8%. After a total of 4 hours of hydrogenation, the yellow hydrogenation solution was rinsed out of the autoclave and the autoclave was then rinsed three times with 50 ml of toluene. The combined toluene solutions were evaporated on a rotary evaporator at 60 ° C./17 mbar. The residue (42 g) became 130-150 ° C bath temperature and 12 mbar distilled. This gave 40.3 g (99.3%) of (R) -α-hydroxy-β, β-dimethyl-γ-butyrolactone (= (R) - (-) - pantolactone), with an optical purity of 92.8 % ee

Beispiele 3-29Examples 3-29

In zu Beispiel 1 analoger Weise wurde eine Katalysatorlösung hergestellt und anschliessend die Hydrierung von Ketopantolacton analog Beispiel 2 durchgeführt. Die Resultate sind in der nachfolgenden Tabelle zusammengefasst:

Figure imgb0008
Figure imgb0009
Figure imgb0010
Figure imgb0011
 A catalyst solution was prepared analogously to Example 1 and the hydrogenation of ketopantolactone was then carried out analogously to Example 2. The results are summarized in the table below:
Figure imgb0008
Figure imgb0009
Figure imgb0010
Figure imgb0011

Beispiel 30Example 30

In einer Glove-Box (O₂-Gehalt <1 ppm) wurde ein 500 ml-Stahlautoklav beladen mit 30 g (0,104 Mol) α-Oxo-γ-(1,3-dioxo-2-isoindolyl) -buttersäure-isopropylester, 110 ml Toluol und einer analog Beispiel 1, aus 165 mg (0,292 mMol) einer 40%igen Tetrabutylammoniumhydroxid-Lösung, 68,3 mg (0,292 mMol) (S)-α-Methoxy-α-trifluormethylphenylessigsäure, 118,4 mg (0,292 mMol) Bis-(1,5-Cyclooctadien)-rhodium(I)-tetrafluoroborat und 164,7 mg (0,292 mMol) (2S,4S)-1-tert-Butoxycarbonyl-4-diphenylphosphino -2-diphenylphosphinomethyl-pyrrolidin hergestellter Katalysatorlösung. Die Hydrierung erfolgte bei einem konstanten Druck von 10 bar H₂, bei 40°C und unter intensivem Rühren während 24 Stunden. Die Hydrierlösung wurde eingedampft, der Rückstand an Kieselgel chromatographiert und die das Produkt enthaltenden Fraktionen eingedampft. Man erhielt 29,5 g (97,4%) (R)-α-Hydroxy-γ-(1,3-dioxo -2-isoindolyl)-buttersäureisopropylester als hellgelbe Kristalle. Smp. 78-82°C. Enantiomere Reinheit 78,5% (gemäss GC-Bestimmung auf einer 21m Kapillarsäule [Se 54] als Camphansäureester). [α] 20 D

Figure imgb0012
= -4,4° (c=1, CH₃OH); optische Reinheit 79,0%.In a glove box (O₂ content <1 ppm) a 500 ml steel autoclave was loaded with 30 g (0.104 mol) of α-oxo-γ- (1,3-dioxo-2-isoindolyl) butyric acid isopropyl ester, 110 ml of toluene and one analogous to Example 1, from 165 mg (0.292 mmol) of a 40% tetrabutylammonium hydroxide solution, 68.3 mg (0.292 mmol) (S) -α-methoxy-α-trifluoromethylphenylacetic acid, 118.4 mg (0.292 mmol ) Bis- (1,5-cyclooctadiene) rhodium (I) tetrafluoroborate and 164.7 mg (0.292 mmol) (2S, 4S) -1-tert-butoxycarbonyl-4-diphenylphosphino -2-diphenylphosphinomethyl-pyrrolidine prepared catalyst solution. The hydrogenation was carried out at a constant pressure of 10 bar H₂, at 40 ° C and with intensive stirring for 24 hours. The hydrogenation solution was evaporated, the residue was chromatographed on silica gel and the fractions containing the product were evaporated. 29.5 g (97.4%) of (R) -α-hydroxy-γ- (1,3-dioxo -2-isoindolyl) butyric acid isopropyl ester were obtained as light yellow crystals. Mp 78-82 ° C. Enantiomeric purity 78.5% (according to GC determination on a 21m capillary column [Se 54] as camphanoic acid ester). [α] 20th D
Figure imgb0012
 = -4.4 ° (c = 1, CH₃OH); optical purity 79.0%.

Claims (10)

  1. A process for the manufacture of chiral rhodium-diphosphine complexes of the general formula



            [Rh(X)(Y)(L0,1 or 2)]1 or 2   I



    wherein X, which can be optionally fixed to a carrier, represents a residue of the formula Z-COO⁻ in which Z signifies a group
    Figure imgb0034
     or aryl, wherein
    R¹, R², R³ =   hydrogen, halogen, lower alkyl, aryl-lower alkyl, perfluoro-C₁₋₂₀-alkyl, aryl or the group -OR , -(CH₂)n-COA or AOC-(CF₂)n, whereby at least one of R¹, R² and R³ represents -OR⁷ or aryl,
    R⁴, R⁵, R⁶ =   hydrogen, halogen, lower alkyl, aryl-lower alkyl, perfluoro-C₁₋₂₀-alkyl, aryl or the group -(CH₂)n-COA or AOC-(CF₂)n,
    R⁷ =   represents hydrogen, lower alkyl, partially or completely halogenated lower alkyl, aryl or aryl-lower alkyl,
    A =   the residue -OR or -NR'₂,
    R =   hydrogen, lower alkyl, aryl, aryl-lower alkyl or a cation,
    R' =   hydrogen, lower alkyl, aryl or aryl-lower alkyl and
    n =   a number 0 to 20, and wherein
    further Y represents a chiral diphosphine ligand and L represents a neutral ligand,
    with the exception of those complexes of formula I in which X, which can be optionally fixed to a carrier, represents a residue of the formula Z-COO⁻ in which Z signifies the group
    Figure imgb0035
     perfluorophenyl, perfluorobiphenyl or a residue of the formula
    Figure imgb0036
     and R¹, R² and R³ represent halogen, lower alkyl, perfluorophenyl, perfluoro-C₁₋₂₀-alkyl, hydrogen or the group -COA or AOC-(CF₂)n- in which A signifies the residue -OR or -NR'₂, whereby, however, at least one of the substituents R¹, R² and R³ signifies fluorine, R signifies hydrogen, lower alkyl or a cation, R' signifies hydrogen or lower alkyl and n signifies a number 1 to 20, whereby the lower alkyl residues have 1-9 carbon atoms and the term aryl stands for optionally substituted aromatic hydrocarbons or aromatic heterocycles with 4-14 carbon atoms.
    characterized by
    a) reacting a rhodium complex of the formula



            [Rh (X) (Lm)]1 or 2   III



    wherein X and L have the above significance and m signifies a number of 1 to 4,
    with a chiral diphosphine ligand, or
    b) reacting a rhodium complex of the formula



            [Rh(Lm+1)]⁺A⁻   IV



    wherein L and m have the above significance and A⁻ represents an anion, especially BF₄ ⁻, ClO₄ ⁻, PF₆ ⁻ or B(C₆H₅)₄ ⁻,
    with a chiral diphosphine ligand and a salt containing the anion X, or
    c) reacting a rhodium-diphosphine complex of the formula



            [Rh (Lp) (Y)]⁺A⁻   V



    wherein L, Y and A⁻ have the above significance and p represents a number of 1 to 3,
    with a salt containing the anion X, or
    d) reacting a chiral rhodium-diphosphine complex of the formula



            [Rh (X¹) (L1 or 2) (Y)]   VI



    wherein X¹ signifies halogen and L and Y have the above significance,
    with a silver salt or thallium salt of the formula



            Ag-X or Tl-X   VII



    wherein X has the above significance.
  2. A process in accordance with claim 1, characterized in that starting materials in which Z represents the group
    Figure imgb0037
     and R¹, R² and R³ have the significances given in claim 1 are used.
  3. A process in accordance with claim 1 or 2, wherein starting materials in which one of the substituents R¹, R² and R³ signifies the residue -OR⁷ and the other two signify fluorine, hydrogen, perfluoro-C₁₋₂₀-alkyl or aryl and R⁷ has the significance given in claim 1 are used.
  4. A process in accordance with claim 1, 2 or 3, characterized in that starting materials in which one of the substituents R¹, R² and R³ represents phenyl and the other two represent fluorine, hydrogen or perfluoro-C₁₋₂₀-alkyl, whereby, however, at least one of them signifies fluorine, are used.
  5. A process in accordance with any one of claims 1 to 4, characterized in that the diphosphine ligand Y in formula I represents a chiral ligand of the general formula
    Figure imgb0038
     wherein R⁸ represents aryl and R⁹ represents the group -CO-R¹⁰, -SO₂-R¹⁰, -PO(R¹⁰)₂ or -PS(R¹⁰)₂ in which R¹⁰ signifies aryl, lower alkyl, di-arylamino, di-lower alkylamino, aryloxy or lower alkoxy, whereby the lower alkyl and, respectively, lower alkoxy residues have 1-9 carbon atoms and the term aryl per se or in aryloxy stands for optionally substituted aromatic hydrocarbons or aromatic heterocycles with 4-14 carbon atoms.
  6. A process in accordance with claim 5, characterized in that R⁹ in the ligand of formula II represents the group -PO(R¹⁰)₂.
  7. A process in accordance with claim 5 or 6, characterized in that in the ligands of formula II R⁸ signifies phenyl, p-tolyl, m-tolyl or 3,5-xylyl and R¹⁰ signifies phenyl, p-tolyl, m-tolyl, p-lower alkoxycarbonylphenyl or tert.butoxy.
  8. The use of the chiral rhodium-diphosphine complexes of formula I manufacturable in accordance with claims 1-7 as catalysts in asymmetric hydrogenations.
  9. The use of the chiral rhodium diphosphine complexes manufacturable in accordance with claims 1-7 for the asymmetric hydrogenation of ketopantolactone to pantolactone.
EP86113271A 1985-10-18 1986-09-26 Chiral rhodium-diphosphine complexes for asymmetrical hydrogenation Expired - Lifetime EP0218970B1 (en)

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US3954821A (en) * 1975-06-30 1976-05-04 E. I. Du Pont De Nemours And Company Carbon dioxide complexes of Rh, Ir, Ni, Pd, and Pt
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US4539411A (en) * 1982-02-05 1985-09-03 Hoffmann-La Roche Inc. Rhodium complexes of chiral phosphines
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